Most patients who develop esophageal adenocarcinoma (EAC) are unaware of the presence of Barrett's esophagus (BE) prior to cancer diagnosis, and 57% have never reported chronic symptoms of gastroesophageal reflux disease (GERD), the current trigger for screening. Thus, the majority of patients who are at risk for the development of EAC are never screened for BE and present with advanced incurable cancer. Our preliminary work has been directed at understanding the relationship between symptoms of GERD, laryngopharyngeal symptoms of reflux, and BE using novel, less invasive methods of screening. We compared in-office unsedated small-caliber endoscopy in a randomized, cross-over trial to conventional sedated endoscopy and established equivalent accuracy in detecting BE with excellent patient tolerability. For the first time, we now have an efficient method to be used for population screening with high acceptance. Dr. Jobe's group has systematically screened otolaryngology patients with cough and hoarseness for BE. Results indicate that the BE prevalence in these subjects, a population not routinely screened, is equivalent to that in a population with classic and chronic GERD symptoms. Finally, in preparation for a multi-center prevalence study, the Barrett's Esophagus Risk Consortium (BERC) was created. BERC consists of 10 centers which are stragically placed across the US, and all participants are internationally recognized experts in BE epidemiology. The next critical step in this work will be to understand the risk for BE an unselected population so that we can narrowly tailor screening efforts. The purpose of this R21 in application is to further develop protocol mechanics in anticipation of the first BERC U-series proposal directed toward the NIDDK Clinical Trials Program with the following specific aims:1) to determine the prevalence of BE within a representative sample of the Nation's primary care population as a surrogate for the US population;2) develop a clinical risk factor probability model that predicts the presence of BE;3) construct and validate a nomogram that incorporates the most potent risk factors as a guide for determining endoscopic screening threshold. This R21 proposal centers on further developing the most optimal methods for subject enrollment, data management, sample size determination, and developing a protocol for multi-center endoscopic screening in primary care patients which will be essential to the eventual success of a large scale trial. PUBLIC HEALTH RELEVANCE This work addresses critical deficits in our understanding of esophageal cancer risk by incorporating a novel screening technology into a consortium study which will for the first time, determine the prevalence and risk of Barrett's esophagus in an unselected U.S. population. This work will enable providers to identify high-risk individuals with Barrett's esophagus, the pre-malignant condition which leads to esophageal cancer, and enroll them into endoscopic surveillance. The end result will be highly focused risk stratification and prevention or improved survival through early detection.